The involvement of NK cells in the antimetastatic effect of the anticoagulant drugs was investigated. The antiplatelet drug prostacyclin (PGI2) and the anticoagulant agents, heparin and warfarin, were efficient in the inhibition of the experimental pulmonary metastases. This antimetastatic effect was observed only in the presence of active NK cells. When NK reactivity of mice was depressed by pretreatment of mice with antiasialo GML serum or cyclophosphomide (Cy), the antimetastatic effect of the anticoagulant drugs was abrogated. Conversely, stimulation of NK cell activity of mice by Poly I:C augmented the antimetastatic effect of the anticoagulant drugs. These date indicate that NK cell activity is crucial for the antimetastatic effects of anticoagulant drugs. Platelet aggregation and fibrin coagulation on the tumor cell membrane surface may be one of the mechanisms responsible for the protection of tumor cells from destruction by NK or other cytotoxic cells. Anticoagulant drugs make tumor cells more vulnerable to the cytotoxic action of blood cells. Adoptively transferred tumoricidal and nontumoricidal peritoneal MPhi elicited by Brewer's thioglycollate medium (TGMPhi) augmented metastases formation in the lungs. These TGMPhi were also able to abrogate antimetastatic effect of Poly I:C treatment. It was in contrast to the peritoneal MPhi elicted by the other tested stimulating media. TGMPhi inoculated i.v. induced intravascular aggregation of the blood leukocytes and severe changes in the vasculature of the lungs which might help tumor cells to extravasate and develop mestastases. These data could explain the failure of attempts of adoptive immunotherapy with tumoricidal TGMPhi.